Cyanobacteria, or "blue-green algae," particularly in freshwater habitats, are recognized to produce an array of potently toxic compounds. Growing evidence indicates that toxigenic cyanobacteria represent a serious concern to human and environmental health. Development of novel approaches will be key to understanding both current and emerging roles of cyanobacterial toxins in environmental health. The proposed research will utilize the zebrafish (Danio rerio) embryo as a toxicological model to investigate toxic or otherwise bioactive metabolites from cyanobacteria. This research will isolate and culture cyanobacteria from two, ecologically unique and distinct freshwater microbial communities, namely the Florida Everglades (and associated waterways in South Florida) and the northern Great Lakes. Cyanobacterial isolates will be screened using the zebrafish embryo as a model of vertebrate development specifically to identify metabolites which interfere with developmental pathways (i.e. developmental toxins). The bioassay will be further utilized to guide initial purification of identified toxins toward the goal of chemical and biological characterization of potentially novel compounds. In addition, the zebrafish model will be used specifically to investigate a ubiquitous class of bacterial toxins, the lipopolysaccharides (LPSs), from cyanobacteria. Though LPSs (or "endotoxins") from Gram-negative heterotophic eubacteria are well described, the same compounds from cyanobacteria have been largely unexplored. However, emerging evidence indicates that cyanobacterial LPSs may have specific effects on certain "detoxifying enzymes," and a subsequent interactive effects with other toxins. Accordingly, the proposed research will further utilize the zebrafish embryo model to test several hypothesis related to the effects of LPSs, specifically from isolated strains of Microcystis, on heavy metal toxicity and accumulation. The proposed research will contribute significantly to our growing understanding of the role of freshwater cyanobacterial toxins in environmental health. [unreadable] [unreadable] [unreadable] [unreadable]